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      Differentiated Thyroid Cancer: Management of Patients with Radioiodine Nonresponsive Disease

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      Author(s): * ,
      Publication date (Electronic):
      Journal: Journal of Thyroid Research
      Publisher: Hindawi Publishing Corporation

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          Abstract

          Differentiated thyroid carcinoma (papillary and follicular) has a favorable prognosis with an 85% 10-year survival. The patients that recur often require surgery and further radioactive iodine to render them disease-free. Five percent of thyroid cancer patients, however, will eventually succumb to their disease. Metastatic thyroid cancer is treated with radioactive iodine if the metastases are radioiodine avid. Cytotoxic chemotherapies for advanced or metastatic noniodine avid thyroid cancers show no prolonged responses and in general have fallen out of favor. Novel targeted therapies have recently been discovered that have given rise to clinical trials for thyroid cancer. Newer aberrations in molecular pathways and oncogenic mutations in thyroid cancer together with the role of angiogenesis in tumor growth have been central to these discoveries. This paper will focus on the management and treatment of metastatic differentiated thyroid cancers that do not take up radioactive iodine.

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          Cancer statistics, 2009.

          A. Jemal, R. Siegel, E. Ward … (2009)
          Each year, the American Cancer Society estimates the number of new cancer cases and deaths expected in the United States in the current year and compiles the most recent data on cancer incidence, mortality, and survival based on incidence data from the National Cancer Institute, Centers for Disease Control and Prevention, and the North American Association of Central Cancer Registries and mortality data from the National Center for Health Statistics. Incidence and death rates are standardized by age to the 2000 United States standard million population. A total of 1,479,350 new cancer cases and 562,340 deaths from cancer are projected to occur in the United States in 2009. Overall cancer incidence rates decreased in the most recent time period in both men (1.8% per year from 2001 to 2005) and women (0.6% per year from 1998 to 2005), largely because of decreases in the three major cancer sites in men (lung, prostate, and colon and rectum [colorectum]) and in two major cancer sites in women (breast and colorectum). Overall cancer death rates decreased in men by 19.2% between 1990 and 2005, with decreases in lung (37%), prostate (24%), and colorectal (17%) cancer rates accounting for nearly 80% of the total decrease. Among women, overall cancer death rates between 1991 and 2005 decreased by 11.4%, with decreases in breast (37%) and colorectal (24%) cancer rates accounting for 60% of the total decrease. The reduction in the overall cancer death rates has resulted in the avoidance of about 650,000 deaths from cancer over the 15-year period. This report also examines cancer incidence, mortality, and survival by site, sex, race/ethnicity, education, geographic area, and calendar year. Although progress has been made in reducing incidence and mortality rates and improving survival, cancer still accounts for more deaths than heart disease in persons younger than 85 years of age. Further progress can be accelerated by applying existing cancer control knowledge across all segments of the population and by supporting new discoveries in cancer prevention, early detection, and treatment.
          Article 0 comments Cited 258 times – based on 0 reviews     Review now
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            BRAF mutation predicts a poorer clinical prognosis for papillary thyroid cancer.

            Mingzhao Xing, William H Westra, Ralph P. Tufano … (2005)
            Use of BRAF mutation in papillary thyroid cancer (PTC) has the potential to improve risk stratification of this cancer. The objective of the study was to investigate the prognostic value of BRAF mutation in patients with PTC. In a multicenter study of 219 PTC patients, data on their clinicopathological characteristics and clinical courses between 1990 and 2004 were retrospectively collected, and their tumor BRAF mutation status was determined. Associations of BRAF mutation with initial tumor characteristics and subsequent recurrence were analyzed. Relationships between the BRAF mutation status and clinicopathological outcomes, including recurrence, were measured. We found a significant association between BRAF mutation and extrathyroidal invasion (P < 0.001), lymph node metastasis (P < 0.001), and advanced tumor stage III/IV (P = 0.007) at initial surgery. This association remained significant on multivariate analysis, adjusting for conventional clinicopathological predictors of recurrence excluding the histological PTC subtype, but was lost when the tumor subtype was included in the model. BRAF mutation was also significantly associated with tumor recurrence, 25 vs. 9% with and without mutation, respectively (P = 0.004), during a median of 15 (interquartile range, 3-29) months of follow-up. This association remained significant on multivariate analysis adjusting for conventional clinicopathological predictors of recurrence, even including the PTC subtype (odds ratio, 4.0; 95% confidence interval, 1.1-14.1; P = 0.03). BRAF mutation was even an independent predictor of recurrence in patients with stage I/II disease, 22 vs. 5% with and without BRAF mutation, respectively (P = 0.002). BRAF mutation was also more frequently associated with absence of tumor I-131 avidity and treatment failure of recurrent disease. In patients with PTC, BRAF mutation is associated with poorer clinicopathological outcomes and independently predicts recurrence. Therefore, BRAF mutation may be a useful molecular marker to assist in risk stratification for patients with PTC.
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              Axitinib is an active treatment for all histologic subtypes of advanced thyroid cancer: results from a phase II study.

              Ezra Cohen, Lee S. Rosen, Everett E. Vokes … (2008)
              Patients with advanced, incurable thyroid cancer not amenable to surgery or radioactive iodine ((131)I) therapy have few satisfactory therapeutic options. This multi-institutional study assessed the activity and safety of axitinib, an oral, potent, and selective inhibitor of vascular endothelial growth factor receptors (VEGFR) 1, 2, and 3 in patients with advanced thyroid cancer. Patients with thyroid cancer of any histology that was resistant or not appropriate for (131)I were enrolled onto a single-arm phase II trial to receive axitinib orally (starting dose, 5 mg twice daily). Objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors was the primary end point. Secondary end points included duration of response, progression-free survival (PFS), overall survival, safety, and modulation of soluble (s) VEGFR. Sixty patients were enrolled. Partial responses were observed in 18 patients, yielding an ORR of 30% (95% CI, 18.9 to 43.2). Stable disease lasting > or = 16 weeks was reported in another 23 patients (38%). responses were noted in all histologic subtypes. Median PFS was 18.1 months (95% CI, 12.1 to not estimable). Axitinib was generally well tolerated, with the most common grade > or = 3 treatment-related adverse event being hypertension (n = 7; 12%). Eight patients (13%) discontinued treatment because of adverse events. Axitinib selectively decreased sVEGFR-2 and sVEGFR-3 plasma concentrations versus sKIT, demonstrating its targeting of VEGFR. Axitinib is a selective inhibitor of VEGFR with compelling antitumor activity in all histologic subtypes of advanced thyroid cancer.
              Article 0 comments Cited 132 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): J Thyroid Res
                Journal ID (iso-abbrev): J Thyroid Res
                Journal ID (publisher-id): JTR
                Title: Journal of Thyroid Research
                Publisher: Hindawi Publishing Corporation
                ISSN (Print): 2090-8067
                ISSN (Electronic): 2042-0072
                Publication date (Print): 2012
                Publication date (Electronic): 28 February 2012
                Volume: 2012
                Electronic Location Identifier: 618985
                Affiliations
                Department of Endocrine Neoplasia and Hormonal Disorders, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1461, Houston, TX 77030, USA
                Author notes
                *Naifa Lamki Busaidy: nbusaidy@ 123456mdanderson.org

                Academic Editor: Mingzhao M. Xing

                Article
                DOI: 10.1155/2012/618985
                PMC ID: 3316972
                PubMed ID: 22530159
                SO-VID: 3d36a959-e8cb-43c7-a2f4-ec2979d3e190
                Copyright © Copyright © 2012 N. L. Busaidy and M. E. Cabanillas.
                License:

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 1 August 2011
                Date revision received : 21 November 2011
                Date accepted : 21 November 2011
                Categories
                Subject: Review Article

                ScienceOpen disciplines: Endocrinology & Diabetes
                Data availability:
                ScienceOpen disciplines: Endocrinology & Diabetes

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